Friday, January 16, 2009
I can now officially say that the off-label marketing of Zyprexa for dementia was criminal. Lilly just admitted to committing a crime in the off-label marketing of the drug for dementia and settled legal charges for a cool $1.4 billion. And there are more cases still on the books.
For a really interesting take on this situation, listen to New York Times reporter Gardiner Harris. You can find his talk embedded in the New York Times story from January 14, 2009, which is linked here. The plea agreement in the latest case is available here.
It is important to remember that pimping Zyprexa for dementia is far from a victimless crime. Antipsychotics, including Zyprexa, have been linked to an increased rate of death in elderly patients and have also been shown to be of little to no more benefit than a placebo in reducing dementia-related symptoms (1, 2). For a disturbing account of the widespread inappropriate use of such medications, read this post and weep.
This is truly a case where lust for profits likely led to the early demise of who-knows-how-many patients. And we're just talking about dementia, not the other cases where Lilly went berzerk with marketing Zyprexa (1, 2).
Blame the Physicians Too: While much of the blame for the overuse of antipsychotics in the elderly can be placed on corporations such as Lilly, it is also true that Lilly does not directly administer the drugs. Physicians need to understand that prescribing drugs which have been found to offer little benefit but are linked to killing patients -- how is that legitimately practicing medicine? First, do no harm?? Yes, I know that dementia is a hell of a difficult condition to handle. But does that mean we should be doling out ineffective and potentially deadly treatments to "manage" persons with dementia. Yes, reps from Lilly (and likely others) wined and dined physicians, "educating" them about the benefits of Zyprexa and other antipsychotics. That's their job -- to positively spin their products. No different than a used car salesperson except that drug reps are typically much better looking.
Doctors need to use critical thinking skills -- you don't just listen to a drug rep or skim a drug-company provided journal article reprint then jump on the Zyprexa bandwagon. How about learning how to evaluate evidence so that junky marketing disguised as science does not persuade you to write inappropriate scripts? Yes, we can be outraged that Lilly and others pimp ineffective and dangerous treatments, but the physicians are the most important link. If they cannot be better educated to understand clinical trial results, and cannot take time to critically review the scientific literature, then this pattern will repeat itself over and over again. It takes tricky pharmaceutical marketing in combination with an audience that is unwilling to think critically for this type of tragedy to occur. And occur again, it will.
Unfortunately, the published scientific literature is quite biased, as negative studies tend to vanish rather than grace the pages of our journals. But it's still a much better idea for prescribers to actually read journals and critically examine their findings, as opposed to relying on marketing alone. Better yet would be for research data on medications (negative and positive) to be available for all to see.
Friday, May 18, 2007
Below are a few articles you may enjoy regarding Covington & Burling's stalwart representation of Big Tobacco, and how they covertly got involved with the "science" surrounding the health effects of secondhand smoke. I highly advise reading them, then thinking about the current Zyprexa controversy.
- Center for Indoor Air Research
- The Latin Project
- Playing with Airline Cabin Science
- More on the "Center for Indoor Air Research"
- Center for Diabetes Studies
- Center for Weight Management Research
- Institute for The Appropriate Marketing of Pharmaceuticals
As pointed out by Ed at Pharmalot, Utah is now added to the list of states suing Lilly over its promotion of Zyprexa. Read some of the statements from Attorney General Mark Shurtleff regarding the lawsuit. The lawsuits just keep stacking up.
It must suck to be Lilly these days. The documents that may incriminate Lilly are just hanging out in full public view. Any enterprising attorney general just needs to get their feet wet by looking through a handful of documents (which can be downloaded here and here) and by perhaps taking a peek at a few posts by your humble correspondent and Philip Dawdy, such as the following:
Tuesday, May 01, 2007
UPDATE: I made an error. I thought that Dr. Tohen held an academic appointment at Mass General -- I was mistaken -- he holds no such appointment. I sincerely apologize for the mistake. Mea culpa. Rather than delete the offending text and leave the impression I am trying to cover my mistake, I will leave it above so that my error can be recognized publicly.
Monday, April 30, 2007
The irony is that Lilly claims that the documents which paint a rather awful picture of its off-label marketing (here, here, here, and here) are taken out of context, yet they refuse to make any additional information available. If the documents are out of context, why don't you provide some context? Indeed, they are suing those who tried to disseminate information pertaining to the drug. And let's also not forget about the email exchange where a Lilly employee discussed ways in which a study casting dispersions on the "safety" of Zyprexa could get deep-sixed through nefarious means.
Friday, April 27, 2007
Once again, Berenson uses the "one paper out of several thousands of documents" approach to depict Lilly as a criminal corporation.Further, it is added
On the heels of intense criticism of the NYT coverage of the Duke rape case and the paper's falling earnings, the Berenson reporting is another example of the Times decline.OK. Here's my challenge. I'd like Drug Wonks or, well, anyone to read the following posts. Read the Lilly documents that are freely available and are linked within said posts. Then talk about how Lilly is a good corporate citizen, and did not promote Zyprexa off-label. Here you go...
- Demented Marketing of Zyprexa?
- Marketing Zyprexa as the New Mood Stabilizer...
- Zyprexa Off-Label Promotion (?)
- Zyprexa Off-Label Marketing (?): Part 2
Wednesday, April 25, 2007
The FDA has questions about a Lilly document from February 2000 in which the company found that patients taking Zyprexa in clinical trials were three and a half times as likely to develop high blood sugar as those who did not take the drug.But worry not, Lilly is claiming the above was just an honest mistake. Kind of a large mistake, eh? After the data were analyzed accurately, then Zyprexa did not appear nearly as risky. Of course, we can be sure Lilly is being honest, just like when they said that they never marketed Zyprexa as a treatment for dementia. Or the time they said that Zyprexa does not cause diabetes. Or maybe when Lilly decided to sell Zyprexa as a "safe, gentle psychotropic." I think you get the point... It is indeed possible that Lilly is being truthful, but I personally doubt it.
That document was not submitted to the agency. But a few months later, Lilly provided data to the FDA that showed almost no difference in blood sugar between patients who took Zyprexa and those who did not.
On a side note, good to see that Alex Berenson is back to writing about Zyprexa.
Monday, April 09, 2007
Above are some pictures of a Swiss Army Knife and a tape measure, both adorned with the Zyprexa name, which can be purchased on Ebay. The Swiss Army Knife was apparently used in the Zyprexa Primary Care marketing campaign as a gift to doctors (see the documentation here). Not sure where the tape measure came from, but I'd bet it was also some sort of marketing tool.
More on the Zyprexa marketing story can be seen here, here, here, and here.
Friday, March 30, 2007
Zyprexa Weighs In (Pun Intended): I posted recently about the "science" of treating "bipolar disorder" in kids. Here's an example of what passes for evidence in the child bipolar treatment world.
An open label (i.e., not placebo-controlled) study indicated that olanzapine (Zyprexa) was “efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder.” By definition, it’s pretty tough to show that your treatment works in the absence of a control group (see research methods 101), so how can it be said that the treatment was efficacious? And as for being “well-tolerated,” keep in mind that the average participant gained five kilograms in eight weeks. That’s not so healthy. If this is what passes for solid evidence, then I suppose bipolar in kids as young as two years old is widely underdiagnosed, and that Zyprexa is a godsend for these poor undertreated children.
Tuesday, March 27, 2007
Well, Brandweek NRX is now reporting that Decision Resources is claiming that the yet-to-be-FDA-approved Acomplia is set to become the new (you guessed it) “gold standard” in treating obesity. Never mind the side effects of depression and anxiety. Text of the press release can be seen here.
It would appear that Decision Resources likes to bandy about the term “gold standard” quite a bit in their reports. In fact, look what happens when you combine “gold standard” with “Decision Resources” – click here.
I’m not really sure what this company actually does and I’m not going to take much time to figure it out. I just find it odd when a company keeps churning out reports labeling various treatments as being the “gold standard” in the absence of any good clinical trial evidence.
Thursday, March 22, 2007
When a company funds a study that finds unfavorable results, they can always deep-six it. But what if someone else conducts the study -- someone you did not fund? Well, a Lilly employee had some interesting thoughts on the matter.
A study was conducted, then presented at a conference. A Lilly employee found out about it, noted that it pointed toward negative safety implications for olanzapine (Zyprexa) and then had some ideas [bold in original, color highlights added]...
If we work on the assumption that this poster WILL be published as a full manuscript soon, our attention needs to turn to how we can minimise its impact on both the global and local level... Where will this paper be published?... Can we stop/delay it? I think it would be very difficult to delay except if one of our scientists could show them that their methodology was flawed...To review, one idea was to find out where the paper might get submitted for publication, then try to influence the editor, as well as sending out a "communications initiative" in an attempt to bias individuals who might review the article to determine its suitability for publication. Or, "influence" the author -- with what? Cash, a baseball bat, hookers and cocaine, what? How does a drug company that did not even sponsor study X call on study X's lead investigator and tell him, "Hey you really shouldn't publish that!" Unbelievable.
Do we know the author? Can we exert any influence? this would be very dangerous as it would be seen as lilly behaving unethically and applies to the below points.
Who sits on the editorial board of the targeted journal? Can we influence them in any way, with respect to the limitations of this methodology? Should we conduct a communications initiative aimed at all influential referees, addressing the above point?
Happy Ending: The author in question has published multiple studies in the area, so either Lilly thought better of their idea to suppress the evidence or their efforts failed miserably. It would seem as if Lilly may wish to hire a Dr. Purple-type character for future efforts (1, 2, 3)??
Source (one of the infamous Zyprexa Documents).
Monday, March 05, 2007
California House Representative Henry Waxman, in his role as chair of the Committee on Oversight and Government Reform, has requested information from Lilly and AstraZeneca regarding their marketing of antipsychotics Zyprexa and Seroquel, respectively. AZ was further asked to provide information regarding its marketing of Actiq, a narcotic lollipop (!) and Fentora, a narcotic lozenge.
Information regarding the safety and purported off-label use of drug coated stents from Boston Scientific and Johnson & Johnson was also requested.
I’d like to point out that bloggers, including Philip Dawdy, myself, and Roy Poses, have written about the shenanigans associated with Zyprexa’s marketing while the major news outlets (except the New York Times) have remained stunningly silent. Perhaps Waxman’s latest move will revive the brain dead media from the fascination with Anna Nicole Smith, Britney Spears, and other stories that are completely unworthy of journalistic attention.
What, is that a blond celebrity with her breasts becoming unhinged from her top? Zy-what? Sero-who? Ugh.
Hat Tip: Furious Seasons.
Saturday, March 03, 2007
You can now listen to the All in the Mind broadcast featuring Philip Dawdy as well as a Lilly spokesperson here. I only caught half of the broadcast yesterday. I'll save my full review of the broadcast until I've heard the full show, but I do feel comfortable saying the following...
The Lilly spokesperson deserves a large salary -- no, make that an enormous salary. His take of blaming mental illness for health problems, while giving Zyprexa a free pass, appears to be a significant detour from reality (1, 2, 3). To make the statements he made while sounding sincere -- well, that deserves applause. I doubt most people could pull off such a performance.
Most folks don't have time to run through the full text of a bunch of journal articles. Here's the quick way to briefly review the current research on the topic of Zyprexa and diabetes. Go to PubMed. Type in olanzapine and diabetes and then read the abstracts of the articles that emerge. Then tell me with a straight face that olanzapine is not related to health problems.
Friday, February 23, 2007
The authors report a case with life-threatening hyperglycemia and acidosis in a patient with no previous diabetic history following treatment with olanzapine. A 35-year-old woman with a history of bipolar affective disorder treated with olanzapine presented with severe diabetic ketoacidosis. She had no prior history of diabetes or risk factors for diabetes. Glycosylated hemoglobin (HbA1c) on admission blood sample suggested that long-term glycemic control had been poor. The authors postulate that treatment with olanzapine precipitated hyperglycemia, an elevated creatine kinase level, and a high amylase level.Perhaps someone should have told these physicians that Zyprexa is a safe, gentle psychotropic that could not possibly induce such nasty side effects.
Wednesday, February 21, 2007
Before reading this piece, please note that Lilly has denied that it markets its products off label.
Martha’s symptoms have been described as much more strongly resembling dementia than either schizophrenia or bipolar, the only two indications for which Zyprexa is FDA approved. According to Alex Berenson, Martha was described as
a widow with adult children "who lives independently and has been your patient for some time." Martha was described as being agitated and having disturbed sleep, but without the symptoms of paranoia or mania that typically marked a person with schizophrenia or bipolar disorder.
Berenson noted that a Lilly spokesperson said that Martha was intended to represent a patient with schizophrenia.
More on Martha: Here is more on Martha, perhaps from the same document examined by Berenson. This document is titled Zyprexa® (olanzapine) Primary Care Q3 Implementation Guide, and it is dated June 2001.
This is Martha. Martha is a widow who lives independently and has been your patient for some time. She is becoming more complicated to manage, and you note increasing agitation. Her sleep is disturbed; she dozes during the day and is up most of the night. Her family has shared their concerns with you, saying, “She thinks we’re trying to take advantage of her.”
Martha’s family doesn’t want to send her to a nursing home, but her agitation and confusion must be addressed. Your goals of treatment for Martha may include reducing her behavioral disturbances without impairing her cognitive functioning.
Does Martha Have Schizophrenia? Upon checking the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia, it appears that Martha does not meet the diagnostic criteria for schizophrenia, despite Lilly’s claims that Martha was intended to represent a patient with schizophrenia.
Later, the same document discusses possible Zyprexa dosage for Martha.
…a starting dose of 5mg – or even 2.5 mg – at bedtime is appropriate.
In schizophrenia trials, Zyprexa is typically dosed at 10-20 mg, not 2.5 mg-5 mg. This also apparently contradicts Lilly’s claim that it was intending Martha to represent a patient with schizophrenia, as it would make little sense for Lilly to recommend a subtherapeutic dose of Zyprexa to physicians.
Under the heading of Back Cover/Close, it is stated:
In summary, doctor, prescribing ZYPREXA is a safe, proven solution for patients like Martha/Michael/Kelly who suffer with mood, thought, and behavioral disturbances. It’s easy to use, and it works [emphasis in original].
Again, note the broad terminology. Rather than discussing bipolar disorder or schizophrenia, for which Zyprexa is indicated, the language of “mood, thought, and behavioral disturbances” is in place, which suggests much a broader application of Zyprexa.
In the same document, a potential question that reps may receive from doctors is mentioned:
With Martha I would just prescribe a cholinesterase inhibitor, such as Aricept. They are supposed to be pretty good with agitation.
Rep: …Why not prescribe ZYPREXA, which has proven efficacy for agitation and related behavioral disturbances [my emphasis], has been on the market for more than 4 years, and has helped over 6 million patients with symptoms just like Martha’s?
In the case of Martha, note again that schizophrenia is not mentioned; instead, “agitation and related behavioral disturbances” are brought to the fore.
FDA Indication for Dementia? In the same document, under the heading of “Helpful Hints,” subheading titled “Martha Spread,” it is stated that
…You will note that on the right-hand side of the spread under the cognition information is a space that has been intentionally left open. Upon launch of the IM [intramuscular] formulation of ZYPREXA, we will be placing a sticker in this spot to announce the new formulation and new indication (agitation associated with dementia) [my emphasis].
Zyprexa was never approved by the FDA for the treatment of dementia, though it would appear from the above quote that Lilly was expecting such approval.
Email Message: To shed further light on the possible off-label promotion of Zyprexa for dementia, further documents were reviewed, including an email issued to “Area Zyprexa Champions,”
Since the diagnosis of our 3 patients in the Zyprexa core message piece are: Martha – dementia,[my emphasis]…can you enlighten us a little more about dementia. We know that we are to describe the symptoms and stay away from diagnoses, but for our own background, can you elaborate on dementia…We are getting a little grief from some of our docs about promoting Zyprexa for dementia [my emphasis], but according to the slides in the audioconference set, there is no FDA approved drug for dementia.
This email clearly indicates that at least some individuals at Lilly were seeing Martha as a case of dementia and that some doctors seemed upset about Zyprexa being promoted for dementia.
Martha’s Symptoms Increase as She Ages: Another document, titled Zyprexa Retail Implementation Guide states under the heading Sales Call, subheading Patient Profile
Martha is a widow you’ve known and treated for several years. As she’s aged, she’s become more complicated to manage – clinically, and at home. These are comments you hear from her family (read testimonials from profile). Your main goal of treatment is to treat her illness and reduce her behavioral disturbances. Do you see patients like Martha?
The comment of her “becoming more complicated to manage” as she’s grown older sounds much more reminiscent of dementia than of schizophrenia, as with schizophrenia, symptom severity is often rather clear at a relatively young age (twenties and thirties) and does not necessarily worsen over time.
Summary: All told, the documents I reviewed appear to paint a picture of Martha being described as a patient with dementia. Her case was then apparently to be described to physicians in primary care settings in an attempt to open their minds to prescribing Zyprexa. Martha’s symptoms do not seem related to schizophrenia; rather, they seem to more strongly resemble symptoms of dementia. In addition, an email indicated that at least some Lilly employees thought of Martha as a patient with dementia and that some physicians were upset that they perceived Zyprexa was being marketed for dementia.
Disclaimer: Please note that I am not equipped to state whether Lilly’s marketing practices regarding Zyprexa were illegal, as the law seems to be pretty unclear on this point.
Of course, whether a practice is legal and whether it is ethical are two different things.
Wednesday, February 14, 2007
I will simply focus on one part of the ruling, in which the judge stated:
The harm faced by Lilly is amplified by the fact that the protected documents which respondents seek to disseminate are segments of a large body of information, whose selective and out-of-context disclosure may lead to confusion in the patient community and undeserved reputational harm –– 'what appears damning may, in context after difficult proof, be shown to be neutral or even favorable to the defendant.Oh, SUCH a bad argument! So unless every single document is released (which Lilly will make sure never happens), then any document released is "out of context." Here's where this line of thinking may lead...
Maybe Lilly can use it to defend themselves regarding Zyprexa and diabetes. "Sure, studies A through Z showed a link between olanzapine and diabetes. But there are other studies which we conducted that put these findings into context. However, we cannot show you said studies because they contain trade secrets. In fact, we insist that all of the earlier published papers linking olanzapine to diabetes be retracted and burned publicly, as they are clearly lacking context."
This trade secrets and out of context thing is blowing my mind. I'm not a lawyer, and I'm glad about that, because I'm not sure I can come to grips with this type of thinking.
This is giving me flashbacks to the British Psychological Society's handling of the Blakemore Brown case and I think I'll need a "safe, gentle psychotropic" to help me handle the stress...
Tuesday, February 13, 2007
The following is some rewording and summarizing of Furious Seasons' recent post on one document related to the Zyprexa-glucose issue:
Lilly had some data indicating that patients who took olanzapine plus mood stabilizers had a mean increase in glucose levels while patients who took placebo plus mood stabilizers showed, on average, a mean decrease in glucose levels.
Dr. Mauricio Tohen of Harvard/Lilly (interesting combination) said that he would like to include the above information when discussing Zyprexa data because he said that the glucose increase was reversible. However, another Lilly official pointed out that since Lilly is aiming for long-term treatment with Zyprexa, pointing out that glucose increases can be reversed when the drug is discontinued does not make much sense. Good point: If the drug has a side effect that can be reversed if you stop taking it, don't tell anyone -- they might not take your drug in the first place!
I'd be interested in tracking down what exactly happened to this data, including whether it ended up hitting the scientific literature in a manner that was accurate, or whether the glucose issue was swept under the carpet. More to come on this one if I can successfully dig up more information.
Mega hat tip to Furious Seasons, who continues his excellent reporting on all things psychiatric, with a special focus on bipolar disorder, schizophrenia, and pharma. I strongly encourage all to read his post on glucose and Zyprexa here.
According to documents reviewed by, and available on, Furious Seasons, it seems that the medical writer has a lot of input, perhaps more than the doctors who were running the study, such as Maricio Tohen.
OK, yes, she is a medical writer, so she should write about medical stuff. I'm not denying that. The writer seems to be doing much more than just summarizing study results -- she seems actively involved in spinning the data: "John [Saunders; Regulatory official for Lilly in Europe], here is how I rewrote the HGHL disposition section to try to soften the "only 66 completers language..."
In this study, 53 of 225 olanzapine patients made it to the end of one year on treatment without dropping out. That is a whopping 23.6%. Placebo patients also appeared to have not fared well (only 9.6% completed the year), but the numbers on efficacy and safety and not discussed in much detail in the document outside of some unfavorable data on glucose (more on that later). The point is that the writer is actively attempting to "soften" the language, likely in an attempt to make olanzapine appear more efficacious.
The medical writer is celarly deeply involved with writing whatever this publication turned out to be. I don't know what happened to this publication. Perhaps it was submitted to some refulatory agency? My concern is that this may be reflective of general practice -- the medical writer "softens" language as appropriate and the doctors whose names appear on the study may actually contribute a relatively minimal amount (or none at all) to the final study writeup.
Maybe I'm reading too much into this?